The main goal of this project is to fully define the fundamental derangement of the physiology of copper that exists in Wilson's Disease and establish if possible the relationship between this disordered copper metabolism and the abnormal gene of Wilson's Disease. Our previous work indicates that the prolonged whole-body retention of copper, found in both homozygote and heterozygote, is associated with or due to faulty biliary excretion of copper. There is demonstrable abnormal retention of copper by the liver in the homozygote and to a less extent in the heterozygote. The question at issue is whether the primary abnormality is defective biliary excretion or diversion of copper to storage from its normal metabolic routes. We propose to seek answers to this question by: 1. Further studies of the bile-specific protein with which most of the biliary copper is associated; we are attempting to produce specific antibody to this protein to facilitate its study. An attempt will be made to purify it and characterize it, and ascertain whether it is deficient or abnormal in Wilsonian Subjects. 2. Studies of the physiology of zinc using radioactive zinc. Since three of the unique copper-proteins of the body - erythrocuprein, hepatocuprein and cerebrocuprein are physically and immunologically identical and contain zinc as well as copper, these studies should provide information not otherwise obtainable on the biological turnover of these storage proteins. 3. The radiozinc studies will also give information on the physiology of zinc in normal subjects and in Wilson's disease.